TY - JOUR

T1 - Within-host genomic evolution of methicillin-resistant Staphylococcus aureus in long-term carriers

AU - Larsen, Tine Graakjær

AU - Samaniego Castruita, Jose Alfredo

AU - Worning, Peder

AU - Westh, Henrik

AU - Bartels, Mette Damkjær

N1 - Publisher Copyright: © 2024, The Author(s).

PY - 2024

Y1 - 2024

N2 - Abstract: Assessing the genomic evolution of Staphylococcus aureus can help us understand how the bacteria adapt to its environment. In this study, we aimed to assess the mutation rate within 144 methicillin-resistant Staphylococcus aureus (MRSA) carriers with a carriage time from 4 to 11 years, including some carriers who belonged to the same households. We found that 23 of the 144 individuals had completely different MRSA types over time and were therefore not long-term carriers of the same MRSA. From the remaining 121 individuals, we performed whole-genome sequencing (WGS) on 424 isolates and then compared these pairwise using core genome multilocus sequence typing (cgMLST) and single-nucleotide polymorphism (SNP) analyses. We found a median within-host mutation rate in long-term MRSA carriers of 4.9 (3.4–6.9) SNPs/genome/year and 2.7 (1.8–4.2) allelic differences/genome/year, when excluding presumed recombination. Furthermore, we stratified the cohort into subgroups and found no significant difference between the median mutation rate of members of households, individuals with presumed continued exposure, e.g., from travel and persons without known continued exposure. Finally, we found that SNPs occurred at random within the genes in our cohort. Key points: • Median mutation rate within long-term MRSA carriers of 4.9 (3.4–6.9) SNPs/genome/year • Similar median mutation rates in subgroups (households, travelers) • No hotspots for SNPs within the genome

AB - Abstract: Assessing the genomic evolution of Staphylococcus aureus can help us understand how the bacteria adapt to its environment. In this study, we aimed to assess the mutation rate within 144 methicillin-resistant Staphylococcus aureus (MRSA) carriers with a carriage time from 4 to 11 years, including some carriers who belonged to the same households. We found that 23 of the 144 individuals had completely different MRSA types over time and were therefore not long-term carriers of the same MRSA. From the remaining 121 individuals, we performed whole-genome sequencing (WGS) on 424 isolates and then compared these pairwise using core genome multilocus sequence typing (cgMLST) and single-nucleotide polymorphism (SNP) analyses. We found a median within-host mutation rate in long-term MRSA carriers of 4.9 (3.4–6.9) SNPs/genome/year and 2.7 (1.8–4.2) allelic differences/genome/year, when excluding presumed recombination. Furthermore, we stratified the cohort into subgroups and found no significant difference between the median mutation rate of members of households, individuals with presumed continued exposure, e.g., from travel and persons without known continued exposure. Finally, we found that SNPs occurred at random within the genes in our cohort. Key points: • Median mutation rate within long-term MRSA carriers of 4.9 (3.4–6.9) SNPs/genome/year • Similar median mutation rates in subgroups (households, travelers) • No hotspots for SNPs within the genome

KW - cgMLST

KW - Genomic evolution

KW - MRSA

KW - Recombination

KW - SNP

KW - Within-host

U2 - 10.1007/s00253-023-12932-3

DO - 10.1007/s00253-023-12932-3

M3 - Journal article

C2 - 38212970

AN - SCOPUS:85182098035

VL - 108

SP - 1

EP - 9

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

SN - 0175-7598

IS - 1

M1 - 95

ER -